Cyclic guanosine 3',5'-monophosphate (abbreviated as cGMP hereafter) was found in urine in rats by D. F. Ashman in 1963. Till now, it has been known that cGMP is distributed broadly in tissues of many animals including human beings. cGMP is biosynthesized from guanosine triphosphate (GTP) by the action of guanylate cyclase.
cGMP has been experimentally confirmed to have various physiological activities. For example, cGMP induces the relaxation of heart muscle and of smooth muscle. Further, it is related to the formation of neuronal synapses, and it acts as a trigger of cell proliferation and it induces the proliferation of lymphocyte.
cGMP is metabolized to physiologically inactive 5'-GMP by the action of cGMP phosphodiesterase (abbreviated as cGMPoPDE hereafter).
Accordingly, the inhibition of the action of cGMP-PDE is considered to be useful for the prevention and/or treatment of diseases induced by enhancement of the metabolism of cGMP, such as hypertension, heart failure, myocardial infarction, angina, atherosclerosis, cardiac edema, renal insufficiency, nephrotic edema, hepatic edema, asthma, bronchitis, dementia, immunodeficiency, pulmonary hypertension.
On the other hand, thromboxane A2 (abbreviated as TXA.sub.2 hereafter) was found as a constituent of the arachidonate cascade, in platelets by M. Hamberg in 1975. TXA.sub.2 is biosynthesized from arachidonic acid released from cell membrane via prostaglandin G.sub.2 and prostaglandin H.sub.2, and rapidly metabolized to inactive thromboxane B.sub.2. TXA.sub.2 is known to induce platelet aggregation and to contract smooth muscle, particularly blood vessel muscle and bronchial muscle. TXA.sub.2 synthetase was isolated and purified from microsome in platelets.
Accordingly, the inhibition of TXA.sub.2 synthetase decreases the biosynthesis of TXA.sub.2, and is useful for the prevention and/or treatment of inflammation, hypertension, thrombosis, arteriosclerosis, cerebral apoplexy, asthma, myocardial infarction, cardiostenosis, cerebral infarction, etc.